Carbon-13 NMR Characterization of an O-Alkylated Derivative of the Theophylline Metabolite 1,3-Dimethyluric Acid

Abstract

The structure of the derivative formed during the reaction of 1,3-dimethyluric acid, the major metabolite of theophylline in humans, with iodopropane was elucidated. GC-MS analysis indicated the presence of a single dipropylated product even though three positional isomers are possible. The stability of the product was lower than anticipated since one of the alkyl groups added was readily removed by acid hydrolysis. Carbon-13 NMR proved to be the most useful technique for establishing the positions of alkylation. Assignment of carbon-13 resonances were consistent with placement of propyl groups on N-7 and on the oxygen at C-8. The structure of the product was assigned as 1,3-dimethyl-7-(1-propyl)-8-(1-propyloxy)xanthine. This O-alkylated structure is unusual since most heterocycles that can exist as lactim-lactam tautomers alkylate primarily on ring nitrogens.     

Reactions of 2,5-di(2-thienyl)pyrroles

We have studied the possible modification of 2,5-di(thienyl)pyrroles with the aim of preparing compounds which can serve as precursors of polymers and monomers showing electrical conductivity and specific photochemical properties. Dedicated to Boris Aleksandrovich Trofimov on his 70^th jubilee. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1356–1365, September, 2008.     

Facile synthesis of 3-aryl 2,3-dihydrobenzofurans via novel domino 1,6-addition/O-alkylation reactions of para-quinone methides

A facile K₂CO₃-promoted novel domino 1,6-addition/O-alkylation reaction of ortho-hydroxyphenylsubstituted p-QMs and diethyl bromomalonate is described. A variety of new 3-aryl 2,3-dihydrobenzofurans were obtained in excellent yields (up to 99%) under simple and mild conditions. The structure of the new compound 3f was determined by single crystal X-ray analysis.     

Enhanced reactivity of secondary hydroxyl groups in the O-alkylation of carbohydrate-related primary-secondaryvic-glycols. Regioselective 2-O-benzylation of 1,3:2,4-di-O-ethylidene-D-glucitol

Partial O-alkylation of 1,3:2,4-di-O-ethylidene-D-glucitol (1a), 1,2-O-isopropylidene-3-O-methyl--D-glucofuranose (1b), andR-(+)-1-O-benzylglycerol (1c) with benzyl chloride in a KOH/DMSO system results in products of monoalkylation at the secondary (4a–c) and at the primary hydroxyl (2a–c) in ratios of over 955 (a), 21 (b), and 11 (c), whereas (±)propane-1,2-diol (1d) gives only the product of 1-O-benzylation (2d). A qualitatively similar result is observed upon O-alkylation of diols (1a–e) with 2-methoxyethanol tosylate.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 776–781, April, 1993.     

An efficient synthesis of pentacyclo[4.2.0.02,5.03,8.04,7]octane-1,4-dicarboxylates

Dialkyl pentacyclo[4.2.0.0^2,5.0^3,8.0^4,7]octane-1,4-dicarboxylates (where alkyl is methyl,iso-propyl, 2-fluoro-2,2-dinitroethyl, or 2,2,2-trinitroethyl) were prepared in high yields by O-alkylation of 1,4-cubanedicarboxylic acid with the corresponding monoalkyl sulfates.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 801–802, April, 1993.     

Influence of phase transfer catalyst structure on selectivity

A concise review is given of systematic studies concerned with the tuning of regio-, frequentio-, chemo-, and diastereoselectivity by the structure or type of phase transfer catalyst.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2094–2101, November, 1995.     

Synthesis and Ion Selectivity of Tetrakis[(N,N-dialkylaminocarbonyl) methoxy]homocalix[4]arenes

An attempted O-alkylation of the flexible macrocycle 1 withN,N-dialkylchloroacetamides in the presence of NaH, K₂CO₃ or Cs₂CO₃ gave only one pure stereoisomer 1,4-alternate-2a–c, while other possible isomers were not observed. In contrast, only an intractable mixture was obtained when Na₂CO₃ was used as base. The structural characterization of these products is discussed. The two-phase solvent extraction data indicated that tetrakis(N,N-dialkylaminocarbonyl) derivatives 2b–c show strong alkali metal cation affinity and the extractabilities are much higher than that for the corresponding calix[4]arene tetraethyl ester 4 and homocalix[4]arene tetraethyl ester 3. High Li⁺ and Na⁺ extractabilities were observed for tetrakis[(N,N-diethylaminocarbonyl) derivative 2b. However, no significant high ion selectivity for alkali metal cations was observed in tetraamide 2b. ¹H-NMR titration of tetraamide 2b with KSCN clearly demonstrates that a 1:1 complex is formed with retention of theoriginal symmetry to be conformationally frozen on the NMR time scale.     

Rapid Synthesis of Alkoxyamine Hydrochloride Derivatives from Alkyl Bromide and N,N′-Di-tert-butoxycarbonylhydroxylamine [(Boc)2NOH]

The conventional route to alkoxyamine hydrochloride derivatives is by reaction of alkyl bromides with N-hydroxyphthalimide or N-hydroxysuccinimide followed by addition of hydrazine and HCl. Transformation of an alkyl bromide to the corresponding alkoxyamine hydrochloride can be accomplished more rapidly in good yields without using hazardous hydrazine by reaction of (Boc)₂NOH (N,N′-di-tert-butoxycarbonylhydroxylamine) and alkyl bromide followed by addition of HCl. Alkoxyamine hydrochlorides are powerful reagents in organic synthesis that can be used to synthesize alkoxyimino derivatives after condensation with a ketone or aldehyde.